具有生物活性的1,3,4-噻二唑并[3,2-a]-1,3,5-三嗪衍生物的合成方法

由1，3，4-噻二唑和1，3，5-三嗪稠合而成的1，3，4-噻二唑并[3，2．a]-1，3，5-三嗪衍生物具有广泛的生物活性，是一类重要的药用物质。本文对其在近二十年的合成方法进行了综述，重点介绍通过1，3，4-噻二唑衍生物为母体的合成方法。参考文献45篇。     

Electron impact mass spectra of 1,3,4-thiadiazolo[3,2-a]pyrimidin-7-one and isomeric-5-one derivatives

The 70 eV electron impact mass spectra of some 1,3,4-thiadiazolo[3,2-a]pyrimidin-7-one and isomeric-5-one derivatives are discussed with the aid of defocused metastable spectra and exact mass measurements. The compounds are shown to be very stable to electron impact and ring contraction reactions are in most cases the characterstic fragmentations. Most importantly, the 7-one derivatives fragment by a retro-Diels–Alder process which does not occur in the 5-one isomers. This provides a diagnostic tool for differentiation between the isomers and for the unequivocal assignment of the structure.     

Condensed 1,3,5-triazines: 1,3,4-Thiadiazolo[3,2-a]-1,3,5-triazines and isoxazolo[2,3-a]-1,3,5-triazines

A convenient route is reported for the synthesis of substituted 1,3,4-thiadiazolo[3,2-a]-1,3,5-triazine-5,7-diones and isoxazolo[2,3-a]-1,3,5-triazines. Condensation of the appropriately substituted 2-amino-1,3,4-thiadiazole and 3-aminoisoxazole with phenoxycarbonyl isocyanate provides the desired target compounds in fair yield.     

Synthesis of Novel Spiro Thiazolo[3,2-a][1,3,5]triazines via 1,3-Dipolar Cycloaddition of Azomethine Ylide

The 1,3‐dipolar cycloaddition of an azomethine ylide generated by a decarboxylative route from sarcosine and acenaphthenequinone to 7‐arylmethylidene‐3‐aryl‐3,4‐dihydro‐2H‐thiazolo[3,2‐a][1,3,5]triazin‐6(7H)‐ones afforded novel dispiro[acenaphthylene‐1,2′‐pyrrolidine]‐3′,7′ ′‐[1,3]thiazolo[3,2‐a][1,3,5]triazines in moderate yields. The structures of the products were determined and characterized thoroughly by NMR, MS, IR, elemental analysis and X‐ray crystallographic analysis. The results of experiment indicated that this 1,3‐dipolar cycloaddition proceeded with high stereoselectivity and regioselectivity.     

Synthesis and conversions of 6-nitro derivatives of 1,3,4-thiadiazolo[3,2-a]pyrimidines

Convenient procedures were developed for the preparation of new 2-R-thio and 2-amino derivatives of 7-methyl-6-nitro-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidines and products of their condensation with aldehydes.     

Single-reactor synthesis of 2R-thio-5,7-dimethyl-1,3,4-thiadiazolo[3,2-a]pyrimidinium perchlorates

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1146–1147, August, 1993.     

Synthesis of derivatives of a new heterocyclic system, 9-oxo-1,3,4-thiadiazolo[3,2-a]pyrido[3,2-e]pyrimidine

Reaction of 2-substituted 5-imino-7-oxo-1,3,4-thiadiazolo[3,2-a]pyrimidines with pentane-2,4-dione in polyphosphoric acid yields 9-oxo-1,3,4-thiadiazolo[3,2-a]pyrido[3,2-e]pyrimidines.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2037–2038, October, 1995.The authors are grateful to V. A. Dorokhov for the skilled preparation of the paper for publication.     

Microwave-Assisted Sequential One-Pot Synthesis of 8-Substituted Pyrazolo[1,5-a][1,3,5]triazines

This paper reports a convenient sequential one-pot approach for the synthesis of an array of 14 pyrazolo[1,5-a][1,3,5]triazines, substituted in C8 by halogen (Br), various functions (CN and CO₂Et) and alkyl or (het)aryl groups. This study confirms the interest of combining the efficient heating obtained under dielectric microwave heating and the achievement of sequential one-pot reactions, avoiding the tedious work-up and purification of intermediate compounds, achieving sustainable synthesis processes. Considering usual conventional methods, this microwave protocol is featured by advantages in terms of yields, reaction times, and convenient gram scale synthesis.     

Differentiation of isomeric 5- and 7-oxo derivatives of tetrahydrothiazolo[3,2-a]pyrimidine by electron impact mass spectrometry

The electron impact mass spectra of two series of 5-oxo-tetrahydro-5H-thiazolo [3,2-a]pyrimidine-6-ethylcarboxylates and 7-oxo-tetrahydro-7H-thiazolo [3,2-a]pyrimidine-6-ethylcarboxylates were measured and fragmentation patterns examined. Structures were assigned from analysis of oxo molecular ion fragmentations. Compounds of the 5-oxo series gave an [M – CO₂C₂H₅]⁺ fragmentation whereas compounds of the 7-oxo series gave three characteristic cleavages. This decomposition was confirmed for one pair of isomers by high-resolution mass spectrometry and unimolecular mass-analysed ion kinetic energy spectrometry. Electron impact mass spectrometry is a convenient method for assigning structures of 5- and 7-oxo regioisomers of tetrahydrothiazolo[3,2-a]pyrimidine-6-carboxylates.     

Some transformations of 2-chloromethyl-7-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one

The reactions of 2-chloromethyl-7-methyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one withtert-butyl hypochlorite and molecular bromine and the replacement of the chlorine atom in the chloromethyl group through the action of piperidine and morpholine were investigated.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 908–910, May, 1994.     

New synthesis of 2-R-thio-7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidines

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, p. 1148, August, 1992.     

Synthesis of 5H-benzimidazo[1,2-a][1,3,4]thiadiazolo[2,3-d][1,3,5]triazin-5-one and 12H-benzimidazo[1,2-a]pyrimido[6,1-d][1,3,5]triazin-12-one,two new heterocyclic ring systems

2-(2,6-Dimethylpyrimidin-4-ylaminobenzimidazole) (VIIa) and 2-(1,3,4-thiadiazol-2-ylamino)benzimidazole (VIIb) underwent a ring-closure reaction with phosgene giving 1,3-dimethyl-12H-benzirnidazo[1,2-a]pyrirnido[6,1][-d][1,3,5]triazin-12-one (IIa) and 5H-benzimidazo[1,2-a][1,3,4]thiadiazolo[2,3-d][1,3,5]triazin-5-one (IIb) two hitherto unknown heterocyclic systems. A convenient synthesis of 2,6-dimethyl-4-aminopyrimidine is described.     

Synthesis of pyrido[3,2-e]pyrrolo[2,1-c][1,2,4]triazines from pyrido[3,2-e][1,2,4]triazine derivatives

In carrying on our interest in heteropolycyclic structures with biological activities, we projected the preparation of compounds containing the pyrido[3,2-e][1,2,4]triazine or pyrido[2,3-b][1,4]triazepine systems. The established synthetic approach for the preparation of latter system led to the triazine derivatives 5a-f while a new bicyclic triazepine structure 6 is accomplished with difficulty. In expanding the pyridotriazine structure, we obtained derivatives of a new tricyclic structure, 5-substituted-6a-ethyloxycarbonyl-5,6,6a,7-tetrahydropyrido[2,3-e]pyrrolo[2,1-c][1,2,4]triazin-9(8H)-ones 8 in which the triazine ring is fused with a pyrrole nucleus. Compounds 5a-f and 8a,b will be tested as potential CNS depressant, antiinflammatory, analgesic and antibacterial agents.     

Synthesis and chemical reactions of 2-RS-methyl-7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidines

The corresponding sulfides have been synthesized starting from 2-chloromethyl-7-methyl-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine and some of their reactions have been studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 549–552, April, 1996.     

2-Substituted 7-amino-1,2,4-triazolo[1,5-a]-[1,3,5]triazines

3-Substituted 5-amino-1-guanyl-1,2,4-triazoles have been obtained which, on reaction with orthoformic ester or 100% formic acid, form 2-substituted 7-amino-1,2,4-triazolo[1,5-a]-[1,3,5]triazines.     

Syntheses based on 2-ethoxycarbonylmethyl-7-methyl-1,3,4-thiadiazolo[3,2-a]pyrimidin-5(5H)-one

2-Ethoxycarbonylmethyl-7-methyl-1,3,4-thiadiazolo[3,2-a]pyrimidin-5(5H)-one containing the active methylene group reacts easily with carbon disulfide and phenyl isothiocyanate in the presence of sodium hydride. Further alkylation of the reaction product by alkyl halides results in the formation of the corresponding 1,3,4-thiadiazolo[3,2-a]pyrimidine derivatives containing a ketene dithioacetal fragment. Deceased. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2371–2373, November, 1998.